A causal relationship between paraproteinemia and neuropathies has been suggested. We studied three patients with chronic sensorimotor polyneuropathy associated with plasma cell dyscrasia and monoclonal gammopathies (IgGK, IgMK, IgAlambda;). Sural nerve biopsies showed mild (2 cases) to moderate loss of myelinated fibers (1 case). Teased single fiber studies showed segmental demyelination-remyelination in two patients. Direct immunofluorescence demonstrated immune deposits of the myelin sheath of the same specificity as the serum paraprotein, IgGK (1 of 3 cases). Treatment with prednisone, melphalan or chlorambucil, and plasma-pheresis resulted in remission (1 case), partial improvement (1 case), or had no effect (1 case), although reduction of monoclonal immunoglobulin occurred in all. To investigate the role the paraproteins might play in the pathogenesis of the neuropathy, patients' serum was injected intraneurally into rat sciatic nerves. None of the animals developed weakness, slowing ofin vitroconduction of sciatic nerve, or significant evidence of demyelination by light- or electron-microscopy or teased single fiber studies 48 hours postinjection. Similar injections of rabbit serum with experimental allergic neuritis (EAN) produced focal segmental demyelination. Our studies employing anin vivobioassay technique failed to establish antimyelin activity of monoclonal immunoglobulin sera.
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